CHOP overexpression sensitizes human non-small cell lung cancer cells to cisplatin treatment by Bcl-2/JNK pathway.

C/EBP homologous protein (CHOP), a 29 kDa cellular protein, plays a role in regulating tumor proliferation, differentiation, metabolism, cell death, and in tumor resistance to chemotherapy. Non-small cell lung cancer (NSCLC) is a tumor of the respiratory system and drug resistance is prevalent among NSCLC clinical cell cultures. Herein, our study elucidated the effect of CHOP on NSCLC cells with cisplatin resistance and its mechanism.

α1-Antitrypsin alleviates inflammation and oxidative stress by suppressing autophagy in asthma.

Background: Asthma is considered an incurable disease, although many advances have been made in asthma treatments in recent years. Therefore, elucidating the pathological mechanisms and seeking novel and effective therapeutic strategies for asthma are urgently needed.

Methods: Airway resistance was measured by whole-body plethysmography.

The methylation profiles of PRDM promoters in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is one of the leading malignant tumors worldwide. Aberrant gene promoter methylation contributes to NSCLC, and PRDM is a tumor suppressor gene family that possesses histone methyltransferase activity. This study aimed to investigate whether aberrant methylation of PRDM promoter is involved in NSCLC.

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract.

Background/aims: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism.

Methods: Primary AECII were isolated from rat lung tissues and exposed to CSE.

Bevacizumab induces A549 cell apoptosis through the mechanism of endoplasmic reticulum stress in vitro.

Aims: To observe the effect of bevacizumab on human A549 cells and explore its mechanism.

Methods: After different concentrations (0 μM, 1 μM, 5 μM, 25 μM) of bevacizumab treating in A549 cells, CCK8 assay detect the impact of bevacizumab on A549 cell proliferation and flow cytometry determine the effect of bevacizumab on human A549 cells apoptosis. Real-time PCR and Western blotting detect the changing expression of the target gene (CHOP, caspase-4, IRE1, XBP-1) on mRNA and Protein level.

Methylation of PRDM2, PRDM5 and PRDM16 genes in lung cancer cells.

Aims: To investigate the changes of expression and methylation status of PRDM2, PRDM5, PRDM16 in lung cancer cells after treatment with demethylation agent.

Methods: A549 (lung adenocarcinoma cell line), HTB-182 (lung squamous cell carcinoma cell line) and HBE (normal bronchial cell line) were treated with 5-aza-2dC. The methylation state of PRDM2, PRDM5, PRDM16 was detected by MSP.

Promoter methylation-mediated downregulation of PRDM5 contributes to the development of lung squamous cell carcinoma.

PRDM5 has been proposed as a tumor suppressor frequently downregualted in tumor. In this study, lung squamous cell carcinoma tissues and adjacent nontumorous normal tissues were collected from 30 patients. PRDM5 expression was detected by reverse transcription polymerase chain reaction and Western blot analysis, DNA methylation of PRDM5 promoter was analyzed by methylation-specific PCR.

[The expression of hypoxia-inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease].

Objective: To observe the expression of hypoxia-inducible factor-lalpha subunit (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive pulmonary disease (COPD).

Methods: Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD group) and 14 without COPD (control group). The ratio of vascular wall area to total vascular area (WA%) and pulmonary artery media thickness (PAMT) was observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.

[The effect of transcription factor KLF2 in expression of gamma-GCS depend on regulation by Nrf2 in lung of rats with chronic obstructive pulmonary disease].

Objective: To study the expression of lung Krüppel-like transcription factor (KLF2/LKLF) in lung tissues of rats with chronic obstructive pulmonary disease (COPD) and the relationship between KLF2 and NF-E2-related factor 2 (Nrf2), and make further explore the effects of KLF2 on the expression of gamma-glutamylcysteine synthetase (gamma-GCS).

Methods: Twenty-two male SD rats were randomly divided into a COPD group (n = 10) and a normal control group (n = 11). The rat model of COPD established by cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS), and lung tissues were obtained.

[The expression and possible role of SENP1 in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension].

Objective: To investigate the dynamic expression and role of SENP1 (SUMO-specific proteases-1) in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension (HPH).

Methods: Forty adult male Wistar rats were randomly divided into 5 groups (n = 8), and exposed to normoxia (Control group) or exposed to hypoxia for 3, 7, 14 or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia.

[The preventative effects of protein tyrosine kinase on the inflammation and airway remondeling in lung of guinea pigs with bronchial asthma].

Aim: To investigate the effects of protein tyrosine kinase on the inflammation and airway remodeling in lung of guinea pigs with bronchial asthma.

Methods: 30 adult male guinea pigs were randomly divided into 3 groups (n=3): control group (C group), asthmatic group(A group)and genistein group (B group). Asthmatic model was established by ovalbumin intraperitoneal injection and ovalbumin inhalation.

[The cooperation of OS-9 and PHDs in hypoxia-induced pulmonary hypertension of rats].

Aim: To investigate the dynamic expression of hypoxia-inducible factor 1alpha, PHDs and OS-9 in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.

Methods: SD rats were randomly divided into 5 groups (n = 8) and exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ hybridization were used to determine the expression of mRNA.

[Roles of NRF2 regulating gamma-glutamylcysteine synthetase in lung of rats with chronic obstructive pulmonary disease].

Aim: To investigate the expression and relationship of gamma-glutamylcysteine synthetase (gamma-GCS) and NF-E2-related factor2 (NRR2) in lung of rat with chronic obstructive pulmonary disease (COPD)in order to elucidate the possible important role of gamma-GCS and NRF2 in pathogenesis of COPD.

Methods: The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The gamma-GCS activity was measured, the expression of gamma-GCS mRNA in lung was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), the protein expressions of NRF2, gamma-GCS in lung were detected by immunohistochemical (IH) and Western blot respectively.

[Reciprocal regulation between hypoxia-inducible factor-1alpha and its prolyl hydroxylases in hypoxic pulmonary hypertension rats].

Objective: To investigate the interaction between hypoxia-inducible factors-1alpha subunit (HIF-1alpha) and its three prolyl hydroxylases (PHD1, PHD2 and PHD3) during the development of rat hypoxic pulmonary hypertension.

Methods: Forty male SD rats were randomly divided into 5 groups and exposed to normoxia (C group) or exposed to hypoxia for 3, 7, 14 or 21 d (H(3), H(7), H(14), H(21) group), respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured.

[Effects of Nrf2 on gamma-glutamylcysteine synthase in lung of guinea pigs with bronchial asthma].

Aim: To investigate the effects of Nrf2 (Nuclear-E2 related factor) on gamma-glutamylcysteine synthase (gamma-GCS) in lung of guinea pigs with bronchial asthma.

Methods: 20 adult male guinea pigs were randomly divided into two groups (n = 10): control group (C group) and asthmatic group (A group), asthmatic model was established by ovalbumin intraperitoneal and ovalbumin inhalation. The reactive oxygen piece (ROS), reduced glutathione (GSH), oxidant glutathione (GSSG) and total GSH in lung tissue were examined respectively.

Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension.

Hypoxia-inducible factor (HIF)-alpha subunits (HIF-1alpha, HIF-2alpha and HIF-3alpha), which play a pivotal role during the development of hypoxia-induced pulmonary hypertension (HPH), are regulated through post-translational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD1, PHD2 and PHD3). PHDs could also be regulated by HIF. But differential and reciprocal regulation between HIF-alpha and PHDs during the development of HPH remains unclear.

[The relationship between the polymorphism of glutamate cysteine ligase modulatory subunit gene and the susceptibility to chronic obstructive pulmonary disease].

Objective: To investigate whether glutamate cysteine ligase modulatory (GCLM) subunit gene polymorphism is associated with susceptibility to chronic obstructive pulmonary disease (COPD), and to study the relationship between polymorphism of GCLM gene with plasma gamma-glutamylcysteine synthetase (gamma-GCS) activity.

Methods: Blood samples of 104 stable phase COPD smokers (COPD group), 124 healthy smokers (C group) and 132 healthy never-smokers (H group) were collected, and then the genotypes of GCLM -588C/T and GCLM -23C/T polymorphism sites were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). The plasma gamma-GCS activity was measured by coupled enzyme procedure.

Transforming growth factor-beta1 induces transdifferentiation of fibroblasts into myofibroblasts in hypoxic pulmonary vascular remodeling.

The muscularization of non-muscular pulmonary arterioles is an important pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-beta1 (TGF-beta1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles.

[Transforming growth factor beta1 correlates inducible nitric oxide synthase in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension].

Objective: To investigate the dynamic expression of transforming growth factor beta(1)(TGF-beta(1)) and inducible nitric oxide synthase (iNOS) in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension (HPH).

Methods: Forty adult male Wistar rats were randomly divided into five groups: a control group (C group) and groups with hypoxia for 3, 7, 14 and 21 days (H(3), H(7), H(14), H(21) group), eight rats per group. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured.

Correlation of HDEFB1 polymorphism and susceptibility to chronic obstructive pulmonary disease in Chinese Han population.

Background: Inherited factors are involved in the development of chronic obstructive pulmonary disease (COPD). This study was designed to investigate the relationship between polymorphisms of HDEFB1 668 C/G and 1654G/A loci and susceptibility to COPD in Chinese Han population.

Methods: After the process of extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers, the loci of genotypes 668C/G and 1654G/A were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and polymerase chain reaction-single strand conformation polymorphism analysis.

[Study on the correlation of interleukin-13 polymorphism and susceptibility to chronic obstructive pulmonary disease in Chinese Han population].

Objective: To investigate the polymorphism of interleukin (IL)-13 gene in Chinese Han population, and to study the possible association of IL-13 polymorphism and the susceptibility to chronic obstructive pulmonary disease (COPD).

Methods: Using genomic DNA extracted with phenol:chloroform:isoamyl alcohol from the blood of 94 healthy smokers and 88 COPD smokers, three single nucleotide polymorphism (SNP) sites in IL-13 gene marked as 1103C/T, 4257G/A, 4738G/A were determined by polymerase chain reaction/restriction fragment length polymorphism analysis or polymerase chain reaction/single strand conformation analysis. In addition, plasma IL-13 concentration was measured by ELISA on 24 healthy smokers and 24 smokers with chronic obstructive pulmonary disease.

[Polymorphism of interleukin-10 gene promoter and its association with susceptibility to chronic obstructive pulmonary disease in Chinese Han people].

Objective: To investigate the polymorphism of interleukin-10 (IL-10) gene promoters in Chinese Han people, and to disclose whether such polymorphism is associated with susceptibility to chronic obstructive pulmonary disease (COPD).

Methods: After the process of extracting genomic DNA from blood of 94 health smokers and 88 COPD smokers by use of phenol-chloroform-isoamyl alcohol, three single nucleotide polymorphism (SNP) sites in IL-10 gene promoter marked as -1082G/A,-819C/T,-592C/A were determined by polymerase chain reaction/restriction fragment length polymorphism analysis.

Results: Eleven different promoter genotypes were detected from all of the 182 smokers, and AA*TT*AA, AA*TC*AC, AA*TC*AA genotypes accounted for about 80% of genotypes in the research subjects.